支气管热成形术对重度哮喘患者气道结构及炎性介质的影响
2020/06/11
摘要
背景：支气管热成形术（BT）是一种用于治疗重度难治性哮喘患者的新技术。支气管镜检查期间对气道壁进行射频治疗，以减少气道重塑。一些临床研究报告受试者BT术后症状有所改善。 然而，目前还未完全阐明BT如何影响气道结构及炎性介质变化。
方法：根据ATS重症哮喘定义标准，本研究入组14名重症哮喘受试者。研究对象在基线和初始BT治疗后6周的支气管镜检查过程中进行了支气管活检。对所得标本进行染色，即α-平滑肌肌动蛋白（α-SMA）抗体；蛋白质基因产物（PGP）9.5，一种特定的神经标记；血管性血友病因子（vWF），血管标记物；白介素-17A（IL-17A）和转化生长因子-β1（TGF-β1）。
结果：BT后α-SMA和PGP9.5的表达明显降低。基线和BT后之间的血管数目没有显著差异。另外，BT气道中IL-17A和TGF-β1生成无影响。α-SMA和PGP9.5的表达变化与肺功能改善无明显相关性。
结论及临床相关性：此研究表明，BT可以减轻重症哮喘患者气道平滑肌数量及气道神经支配，而对脉管系统及气道中炎性介质的产生无影响。
Effect of Bronchial Thermoplasty on Structural Changes and Inflammatory Mediators in the Airways of Subjects With Severe Asthma
Tomohiro Ichikawa,Alice Panariti,Severine Audusseau,Andrea Karen Mogas, Ronald Olivenstein, Jamila Chakir, Michel Laviolette, Zoulfia Allakhverdi, Saba Al Heialy, James G Martin, Qutayba Hamid.
Abstract
Background：Bronchial thermoplasty (BT) is a novel technique used in the treatment of subjects with severe refractory asthma. Radiofrequency is provided to airway walls during bronchoscopy in order to reduce airway remodeling. Several clinical studies have reported an improvement in subjects' symptoms following BT. However, how BT affects the airway architectures and inflammatory mediators in the airways has not been yet fully elucidated.
Methods：Fourteen subjects with severe asthma were recruited in this study according to the criteria of ATS severe asthma definition. The study subjects undertook bronchial biopsy during the bronchoscopy procedure at baseline and 6 weeks after the initial BT treatment. The obtained samples were stained with antibodies for α-smooth muscle actin (α-SMA); protein gene product (PGP) 9.5, a specific nerve marker; von Willebrand factor (vWF), a marker for blood vessels; interleukin-17A (IL-17A) and transforming growth factor-β1 (TGF-β1).
Results：The expression of α-SMA and PGP9.5 were significantly reduced post-BT. There was no significant difference in the number of blood vessels between baseline and post-BT. In addition, BT did not affect the production of IL-17A and TGF-β1 in the airways. The changes in the expression of α-SMA and PGP9.5 had no significant correlation with the improvement of pulmonary function.
Conclusion and Clinical Relevance：This study suggests that BT reduces airway smooth muscle mass and the airway innervation without affecting vasculature and the production of inflammatory mediators in the airways of subjects with severe asthma.
背景：支气管热成形术（BT）是一种用于治疗重度难治性哮喘患者的新技术。支气管镜检查期间对气道壁进行射频治疗，以减少气道重塑。一些临床研究报告受试者BT术后症状有所改善。 然而，目前还未完全阐明BT如何影响气道结构及炎性介质变化。
方法：根据ATS重症哮喘定义标准，本研究入组14名重症哮喘受试者。研究对象在基线和初始BT治疗后6周的支气管镜检查过程中进行了支气管活检。对所得标本进行染色，即α-平滑肌肌动蛋白（α-SMA）抗体；蛋白质基因产物（PGP）9.5，一种特定的神经标记；血管性血友病因子（vWF），血管标记物；白介素-17A（IL-17A）和转化生长因子-β1（TGF-β1）。
结果：BT后α-SMA和PGP9.5的表达明显降低。基线和BT后之间的血管数目没有显著差异。另外，BT气道中IL-17A和TGF-β1生成无影响。α-SMA和PGP9.5的表达变化与肺功能改善无明显相关性。
结论及临床相关性：此研究表明，BT可以减轻重症哮喘患者气道平滑肌数量及气道神经支配，而对脉管系统及气道中炎性介质的产生无影响。
（中日友好医院呼吸与危重症医学科 张鑫 摘译 林江涛 审校）
（Clinical Trial Respir Med. 2019 Apr;150:165-172. doi: 10.1016/j.rmed.2019.03.005. Epub 2019 Mar 20.）
（Clinical Trial Respir Med. 2019 Apr;150:165-172. doi: 10.1016/j.rmed.2019.03.005. Epub 2019 Mar 20.）
Effect of Bronchial Thermoplasty on Structural Changes and Inflammatory Mediators in the Airways of Subjects With Severe Asthma
Tomohiro Ichikawa,Alice Panariti,Severine Audusseau,Andrea Karen Mogas, Ronald Olivenstein, Jamila Chakir, Michel Laviolette, Zoulfia Allakhverdi, Saba Al Heialy, James G Martin, Qutayba Hamid.
Abstract
Background：Bronchial thermoplasty (BT) is a novel technique used in the treatment of subjects with severe refractory asthma. Radiofrequency is provided to airway walls during bronchoscopy in order to reduce airway remodeling. Several clinical studies have reported an improvement in subjects' symptoms following BT. However, how BT affects the airway architectures and inflammatory mediators in the airways has not been yet fully elucidated.
Methods：Fourteen subjects with severe asthma were recruited in this study according to the criteria of ATS severe asthma definition. The study subjects undertook bronchial biopsy during the bronchoscopy procedure at baseline and 6 weeks after the initial BT treatment. The obtained samples were stained with antibodies for α-smooth muscle actin (α-SMA); protein gene product (PGP) 9.5, a specific nerve marker; von Willebrand factor (vWF), a marker for blood vessels; interleukin-17A (IL-17A) and transforming growth factor-β1 (TGF-β1).
Results：The expression of α-SMA and PGP9.5 were significantly reduced post-BT. There was no significant difference in the number of blood vessels between baseline and post-BT. In addition, BT did not affect the production of IL-17A and TGF-β1 in the airways. The changes in the expression of α-SMA and PGP9.5 had no significant correlation with the improvement of pulmonary function.
Conclusion and Clinical Relevance：This study suggests that BT reduces airway smooth muscle mass and the airway innervation without affecting vasculature and the production of inflammatory mediators in the airways of subjects with severe asthma.
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